The goal of this project has been (1) to develop the utility and improve the stereocontrol of intramolecular [2+2] photochemical cycloaddition reactions, (2) develop new cyclobutane fragmentation sequences to improve the versatility and importance of intramolecular photocycloadditions, (3) develop new methods for the rapid, efficient preparation of highly substituted and functionalized photocycloaddition substrates and (4) demonstrate the synthetic potential of photocycloaddition-cyclobutane modification strategies through their application to the total synthesis of biologically active and structurally complex naturally occurring materials. Primary emphasis has been placed on the use of intramolecular photocycloadditions in the control of stereochemistry and the formation of quaternary carbon centers in 3 atom tethered enone-olefin substrates (1,6- enone olefins). This application outlines a continuing extension of these studies in the context of the total synthesis of ginkgolide B,3-5 lubiminol and cyclooctane natural products such as ceroplastol II as well as an expansion into the investigation of stereochemical control in photocycloadditions with 4 atom tethers (1,7 enone-olefins) in the context of synthetic approaches to taxusin, magellaninone, and serratinine. The studies proposed in this application will add significantly to the increased understanding of the stereochemical outcome of intramolecular photochemical cycloaddition reactions which has already been realized from our earlier studies. Double asymmetric induction from stereogenic centers on the tether of 1,6 and 1,7 dienes will be probed. The radical fragmentation sequences will allow increased flexibility in the modification of photocycloaddition products: a critical element in the successful application of [2+2] photocycloadditions in synthesis. Studies on the functionalized zinc-copper reagent conjugate addition-cyclization reactions will dramatically improve the efficiency for the construction of highly functionalized and substituted cyclopentenones and cyclohexenones and will provide rapid entry to systems which would be virtually inaccessible by other methods. The investigation of the use of chiral auxiliaries on 2-carboalkoxycyclopent-2-en-1-ones to induce asymmetry in photocycloadditions could potentially lead to reactions which will dramatically increase molecular complexity while generating a single enantiomeric product. The asymmetric propiolate anion could have a major impact on the preparation of enantiomerically enriched acetylenic alcohols in a direct sequence, a process which has been circumvented previously by multistep sequences. The combination of a zinc homoenolate cyclization- Diels-Alder tandem sequence could allow for a rapid increase in molecular complexity: formation of four new carbon-carbon bonds in a single reaction.